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首页> 外文期刊>Addiction biology >Stress vulnerability promotes an alcohol‐prone phenotype in a preclinical model of sustained depression
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Stress vulnerability promotes an alcohol‐prone phenotype in a preclinical model of sustained depression

机译：压力脆弱性在持续抑郁症的临床前模型中促进酒精易发的表型

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Abstract Major depression and alcohol‐related disorders frequently co‐occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat–induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self‐administration (SA). Male Wistar rats were subjected to social defeat (five episodes) and prolonged social isolation (~12?weeks) and subsequently classified as SDPS‐prone or SDPS‐resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction, and cue‐induced reinstatement of alcohol seeking were examined in the two subpopulations. SDPS‐prone animals showed increased alcohol SA, heightened motivation to acquire alcohol, persistent alcohol seeking despite alcohol unavailability, signs of extinction resistance, and increased cue‐induced relapse; the latter could be blocked by the α 2 adrenoreceptor agonist guanfacine. In SDPS‐resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol seeking and alcohol taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD‐like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long‐term.
机译：摘要经常共同发生摘要主要抑郁和与酒精相关的疾病。抑郁症严重程度对同经醇使用障碍（AUD）的严重性和持续性，对疾病预后的严重影响。在这里，我们调查了抑郁症是否能够在临床前等级推动对澳元的倾向。我们使用社会失败诱导的持续压力（SDP）慢性抑郁症模型与操作饮酒自我管理（SA）组合。雄性Wistar大鼠受到社会失败（五集），长期社会隔离（〜12？周），随后根据他们的情感和认知性能归类为SDPS-Prone或SDPS - 弹性。在两种亚群中检查了使用术语，获取，动机，灭绝和提示诱导的酒精饲料恢复。 SDPS-Prone动物表明酒精SA升高，动机提高了饮酒，持续的酒精尽管酒精不可用，消化性抗性迹象，以及增加的Cue诱导的复发;后者可以被α2肾上腺菌属激动剂的胍丰菌梗阻阻断。在SDPS - 弹性大鼠中，在不影响任何其他酒精寻求和酒精采取的任何其他措施的情况下，在社会失败之前提高了酒精SA。我们的数据显示，抑郁症的一句话对酗酒的脆弱性，在人类成瘾者中看到的酒精依赖模式，并且在很大程度上可以在很大程度上保护抑郁症免受澳元表型的发展。此外，我们的数据表明，单独的压力暴露，独立于抑郁症状，长期改变酒精摄入量。

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